Monday, 13 March 2017

New autoantigen in Astrocyte

Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and is upregulated in reactive astrocytes.
Cristofanilli M, Gratch D, Pagano B, McDermott K, Huang J, Jian J, Bates D, Sadiq SA.Mult Scler. 2016 Dec 1:1352458516684022

BACKGROUND: Transglutaminase-6 (TGM6), a member of the transglutaminase enzyme family, is found predominantly in central nervous system (CNS) neurons under physiological conditions. It has been proposed as an autoimmune target in cerebral palsy, gluten-sensitive cerebellar ataxia, and schizophrenia.
OBJECTIVE:To investigate TGM6 involvement in multiple sclerosis (MS).
METHODS: Antibody levels against TGM6 (TGM6-IgG) were measured in the cerebrospinal fluid (CSF) of 62 primary progressive multiple sclerosis (PPMS), 85 secondary progressive multiple sclerosis (SPMS), and 50 relapsing-remitting multiple sclerosis (RRMS) patients and 51 controls. TGM6 protein expression was analyzed in MS brain autopsy, murine experimental autoimmune encephalomyelitis (EAE), and cultured astrocytes.
RESULTS: CSF levels of TGM6-IgG were significantly higher in PPMS and SPMS compared to RRMS and controls. Notably, patients with clinically active disease had the highest TGM6-IgG levels. Additionally, brain pathology revealed strong TGM6 expression by reactive astrocytes within MS plaques. In EAE, TGM6 expression in the spinal cord correlated with disease course and localized in reactive astrocytes infiltrating white matter lesions. Finally, knocking down TGM6 expression in cultured reactive astrocytes reduced their glial fibrillary acidic protein (GFAP) expression.
CONCLUSION: TGM6-IgG may be a candidate CSF biomarker to predict and monitor disease activity in progressive MS patients. Furthermore, TGM6 expression by reactive astrocytes within both human and mouse lesions suggests its involvement in the mechanisms of glial scar formation.


So yet another autoantigen to cause MS and this time it is Transglutaminase-6. (TGM) are a family of enzymes involved primarily in protein crosslinking. Their altered expression induced by pathologic stimuli is thought to play a major role in cell injury and death in a number of chronic neurodegenerative conditions. Transglutaminase-6 (TGM6), which is expressed predominantly by neuronal cells under normal condition in this study they find it in astrocytes in MS and EAE. In the study they knock down the TGM6 and there is less astrocyte activity. Is this a treatment for astrocytes?

First things first, we have been here before and they have all fallen by the wayside, so they have to be repeated.

However looking at the data you can instantly see it is just a subset of people who have a response and some people with primary and secondary progressive MS have a high response. But there is such massive overlap between health and MS, it is going to be a dud.

There is clearly no predictive value and one may guess that it is a consequence rather than a cause of damage. 


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